双醋瑞因对小鼠肉芽肿诱导的软骨破坏的影响。

Effects of diacerhein on granuloma induced cartilage breakdown in the mouse.

作者信息

Moore A R, Greenslade K J, Alam C A, Willoughby D A

机构信息

Department of Experimental Pathology, William Harvey Research Institute, London, U.K.

出版信息

Osteoarthritis Cartilage. 1998 Jan;6(1):19-23. doi: 10.1053/joca.1997.0088.

DOI:10.1053/joca.1997.0088

PMID:9616435

Abstract

OBJECTIVE

Diacerhein, an anti-osteoarthritic agent, was tested for its ability to suppress synthesis of proinflammatory cytokines in a model of granuloma-induced cartilage breakdown.

DESIGN

50 TO mice received a subcutaneous implant of cotton-wrapped rat femoral head cartilage for a period of 2 weeks. Animals (N = 10/group) were dosed daily with either 6 mg/kg p.o. diclofenac or diacetylrhein at 5, 15 or 50 mg/kg p.o. in 0.1.ml 1% gum tragacanth which served as a control. Implanted cartilages were assayed for glycosaminoglycan (GAG) and hydroxyproline content. The surrounding granulomas were assayed for interleukin-1 alpha (IL-1 alpha), tumour necrosis factor-alpha (TNF-alpha) and IL-6. Statistical analysis was by Mann-Whitney U test.

RESULTS

Diclofenac had no significant effect on GAG or hydroxyproline content of implanted cartilage or on granuloma cytokine concentrations. Diacerhein protected implanted cartilages against hydroxyproline loss, implanted control cartilages contained 220 micrograms hydroxyproline compared with diacerhein at 5, 15 and 50 mg/kg which produced a 21, 16 and 59% decrease in hydroxyproline loss compared with non-implanted controls (P < 0.05, 0.05 and 0.001) respectively. Diacerhein also protected against GAG loss at 5 mg/kg and 50 mg/kg, control cartilages contained 134 micrograms GAG compared with diacerhein at 5 mg/kg and 50 mg/kg which produced a 24 and 38% decrease in GAG loss respectively (P < 0.05 for both). Diacerhein significantly reduced granuloma interleukin-1 alpha content at 5 mg/kg (control level of 2.4 micrograms/ml reduced by 58%; P < 0.05), reduced TNF-alpha at 5 mg/kg and 15 mg/kg (reduced by 61%: P < 0.01 and 49%: P < 0.05 respectively; control level of 469 pg/ml) and reduced IL-6 at 15 mg/kg and 50 mg/kg (control level of 537 pg/ml reduced by 60 and 51%, respectively; P < 0.01 for both).

CONCLUSIONS

The mechanism of the chondroprotective effects of diacerhein is not understood but may be explained by a reduction in the concentrations of proinflammatory cytokines.

摘要

目的

在肉芽肿诱导的软骨破坏模型中，测试抗骨关节炎药物双醋瑞因抑制促炎细胞因子合成的能力。

设计

50只小鼠皮下植入包裹有大鼠股骨头软骨的棉球，持续2周。动物（每组N = 10只）每日口服给药，分别为6 mg/kg双氯芬酸或5、15或50 mg/kg双醋瑞因，溶于0.1 ml 1%刺梧桐树胶中作为对照。对植入的软骨进行糖胺聚糖（GAG）和羟脯氨酸含量测定。对周围肉芽肿进行白细胞介素-1α（IL-1α）、肿瘤坏死因子-α（TNF-α）和IL-6测定。采用曼-惠特尼U检验进行统计学分析。

结果

双氯芬酸对植入软骨的GAG或羟脯氨酸含量以及肉芽肿细胞因子浓度无显著影响。双醋瑞因可保护植入软骨防止羟脯氨酸丢失，植入的对照软骨含220 μg羟脯氨酸，而5、15和50 mg/kg双醋瑞因组与未植入对照相比，羟脯氨酸丢失分别减少21%、16%和59%（P < 0.05、0.05和0.001）。双醋瑞因在5 mg/kg和50 mg/kg时还可防止GAG丢失，对照软骨含134 μg GAG，而5 mg/kg和50 mg/kg双醋瑞因组GAG丢失分别减少24%和38%（两者P < 0.05）。双醋瑞因在5 mg/kg时显著降低肉芽肿白细胞介素-1α含量（对照水平2.4 μg/ml降低58%；P < 0.05），在5 mg/kg和15 mg/kg时降低TNF-α（分别降低61%：P < 0.01和49%：P < 0.05；对照水平469 pg/ml），在15 mg/kg和50 mg/kg时降低IL-6（对照水平537 pg/ml分别降低60%和51%；两者P < 0.01）。